Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG)...
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2010
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13510088_v17_n3_p611_Ahtiainen http://hdl.handle.net/20.500.12110/paper_13510088_v17_n3_p611_Ahtiainen |
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paper:paper_13510088_v17_n3_p611_Ahtiainen2023-06-08T16:10:59Z Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels bromocriptine chorionic gonadotropin beta subunit cyclin D1 cyclin dependent kinase 4 estradiol luteinizing hormone mifepristone progesterone retinoblastoma protein tamoxifen transcription factor E2F1 chorionic gonadotropin beta subunit cyclin dependent kinase 4 luteinizing hormone progesterone prolactin animal cell animal experiment animal model article cell culture controlled study female gonadectomy histology hypophysis tumor immunohistochemistry mouse nonhuman ovary progesterone release prolactinoma radioimmunoassay rat reverse transcription polymerase chain reaction transgenic mouse tumor growth analysis of variance animal blood cell proliferation cytology genetics hypophysis hypophysis tumor metabolism prolactinoma Analysis of Variance Animals Cell Proliferation Cells, Cultured Chorionic Gonadotropin, beta Subunit, Human Cyclin-Dependent Kinase 4 Female Luteinizing Hormone Mice Mice, Transgenic Pituitary Gland Pituitary Neoplasms Progesterone Prolactin Prolactinoma Radioimmunoassay Reverse Transcriptase Polymerase Chain Reaction The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG) β-subunit. The LH/CG bioactivity is elevated in the mice, with consequent highly stimulated ovarian progesterone (P4) production, in the face of normal estrogen secretion. Curiously, despite normal estrogen levels, large prolactinomas developed in these mice, and we provide here several lines of evidence that the elevated P4 levels are involved in the growth of these estrogen-dependent tumors. The antiprogestin mifepristone inhibited tumor growth, and combined postgonadectomy estradiol/P4 treatment was more effective than estrogen alone in inducing tumor growth. Evidence for direct growth-promoting effect of P4 was obtained from cultures of primary mouse pituitary cells and rat somatomammotroph GH3 cells. The mouse tumors and cultured cells revealed stimulation of the cyclin D1/cyclin-dependent kinase 4/retinoblastoma protein/transcription factor E2F1 pathway in the growth response to P4. If extrapolated to humans, and given the importance of endogenous P4 and synthetic progestins in female reproductive functions and their pharmacotherapy, it is relevant to revisit the potential role of these hormones in the origin and growth of prolactinomas. © 2010 Society for Endocrinology. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13510088_v17_n3_p611_Ahtiainen http://hdl.handle.net/20.500.12110/paper_13510088_v17_n3_p611_Ahtiainen |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
bromocriptine chorionic gonadotropin beta subunit cyclin D1 cyclin dependent kinase 4 estradiol luteinizing hormone mifepristone progesterone retinoblastoma protein tamoxifen transcription factor E2F1 chorionic gonadotropin beta subunit cyclin dependent kinase 4 luteinizing hormone progesterone prolactin animal cell animal experiment animal model article cell culture controlled study female gonadectomy histology hypophysis tumor immunohistochemistry mouse nonhuman ovary progesterone release prolactinoma radioimmunoassay rat reverse transcription polymerase chain reaction transgenic mouse tumor growth analysis of variance animal blood cell proliferation cytology genetics hypophysis hypophysis tumor metabolism prolactinoma Analysis of Variance Animals Cell Proliferation Cells, Cultured Chorionic Gonadotropin, beta Subunit, Human Cyclin-Dependent Kinase 4 Female Luteinizing Hormone Mice Mice, Transgenic Pituitary Gland Pituitary Neoplasms Progesterone Prolactin Prolactinoma Radioimmunoassay Reverse Transcriptase Polymerase Chain Reaction |
| spellingShingle |
bromocriptine chorionic gonadotropin beta subunit cyclin D1 cyclin dependent kinase 4 estradiol luteinizing hormone mifepristone progesterone retinoblastoma protein tamoxifen transcription factor E2F1 chorionic gonadotropin beta subunit cyclin dependent kinase 4 luteinizing hormone progesterone prolactin animal cell animal experiment animal model article cell culture controlled study female gonadectomy histology hypophysis tumor immunohistochemistry mouse nonhuman ovary progesterone release prolactinoma radioimmunoassay rat reverse transcription polymerase chain reaction transgenic mouse tumor growth analysis of variance animal blood cell proliferation cytology genetics hypophysis hypophysis tumor metabolism prolactinoma Analysis of Variance Animals Cell Proliferation Cells, Cultured Chorionic Gonadotropin, beta Subunit, Human Cyclin-Dependent Kinase 4 Female Luteinizing Hormone Mice Mice, Transgenic Pituitary Gland Pituitary Neoplasms Progesterone Prolactin Prolactinoma Radioimmunoassay Reverse Transcriptase Polymerase Chain Reaction Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| topic_facet |
bromocriptine chorionic gonadotropin beta subunit cyclin D1 cyclin dependent kinase 4 estradiol luteinizing hormone mifepristone progesterone retinoblastoma protein tamoxifen transcription factor E2F1 chorionic gonadotropin beta subunit cyclin dependent kinase 4 luteinizing hormone progesterone prolactin animal cell animal experiment animal model article cell culture controlled study female gonadectomy histology hypophysis tumor immunohistochemistry mouse nonhuman ovary progesterone release prolactinoma radioimmunoassay rat reverse transcription polymerase chain reaction transgenic mouse tumor growth analysis of variance animal blood cell proliferation cytology genetics hypophysis hypophysis tumor metabolism prolactinoma Analysis of Variance Animals Cell Proliferation Cells, Cultured Chorionic Gonadotropin, beta Subunit, Human Cyclin-Dependent Kinase 4 Female Luteinizing Hormone Mice Mice, Transgenic Pituitary Gland Pituitary Neoplasms Progesterone Prolactin Prolactinoma Radioimmunoassay Reverse Transcriptase Polymerase Chain Reaction |
| description |
The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG) β-subunit. The LH/CG bioactivity is elevated in the mice, with consequent highly stimulated ovarian progesterone (P4) production, in the face of normal estrogen secretion. Curiously, despite normal estrogen levels, large prolactinomas developed in these mice, and we provide here several lines of evidence that the elevated P4 levels are involved in the growth of these estrogen-dependent tumors. The antiprogestin mifepristone inhibited tumor growth, and combined postgonadectomy estradiol/P4 treatment was more effective than estrogen alone in inducing tumor growth. Evidence for direct growth-promoting effect of P4 was obtained from cultures of primary mouse pituitary cells and rat somatomammotroph GH3 cells. The mouse tumors and cultured cells revealed stimulation of the cyclin D1/cyclin-dependent kinase 4/retinoblastoma protein/transcription factor E2F1 pathway in the growth response to P4. If extrapolated to humans, and given the importance of endogenous P4 and synthetic progestins in female reproductive functions and their pharmacotherapy, it is relevant to revisit the potential role of these hormones in the origin and growth of prolactinomas. © 2010 Society for Endocrinology. |
| title |
Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| title_short |
Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| title_full |
Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| title_fullStr |
Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| title_full_unstemmed |
Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| title_sort |
enhanced lh action in transgenic female mice expressing hcgβ-subunit induces pituitary prolactinomas; the role of high progesterone levels |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13510088_v17_n3_p611_Ahtiainen http://hdl.handle.net/20.500.12110/paper_13510088_v17_n3_p611_Ahtiainen |
| _version_ |
1768545569921302528 |